Early Treatment May Delay Atherosclerosis in Familial Hypercholesterolemia

Jeff Craven

March 09, 2022

Patients with familial hypercholesterolemia (FH) who start lipid-lowering treatment earlier in life may reduce their cardiovascular risk, compared with those who don't begin treatment early, according to results of a recent meta-analysis.

They showed a difference in the carotid intima-media thickness (IMT) between patients with and without FH that increased with age, but there was also a difference in IMT seen among patients with FH who started treatment early, compared with untreated patients with FH, Kika van Bergen en Henegouwen, of the departments of pediatrics and epidemiology and data science at Amsterdam University Medical Center, and colleagues wrote in their report, published in the Journal of Clinical Lipidology.

"The fact that the difference in IMT increases with age between FH patients and unaffected controls, and is more pronounced in studies with untreated FH patients than in studies with treated patients, suggests that starting treatment already at a young age in patients with FH is preferred," the researchers wrote. "However, despite treatment, IMT in treated FH patients is still thicker in comparison to subjects without FH."

The researchers identified 42 studies with among patients with FH and healthy control groups across the MEDLINE, EMBASE and Trials.gov databases up to a cutoff date of April 2020, with 39 studies specifically examining carotid IMT, 2 studies evaluating carotid and femoral IMT, and 1 study evaluating femoral IMT alone. Overall, the researchers examined IMT measurements in 3796 patients with FH and 2363 control group participants.

Although data on age and gender for FH and control groups were not available in 6 studies, the mean age ranged from 9 to 57 years for patients with FH and from 8 to 61 years in the control group. Men comprised just under half of both the FH and control groups.

The mean between-group difference in carotid IMT in 34 studies was 0.11 mm (95% CI, 0.06 - 0.15 mm; P < .001) for patients with FH, compared with the control group, while the mean difference in femoral IMT in three studies was 0.47 mm (95% CI, 0.19 - 0.74 mm; P < .001) between FH and control groups.

In 13 studies in which data on differences between partly treated and untreated FH were available, there was a significant between-group difference in carotid IMT with partly treated patients with FH, compared with the control group (0.05 mm; 95% CI, 0.03 - 0.08 mm; P < .001), but a larger mean between-group difference in carotid IMT among untreated patients with FH, compared with a control group (0.12 mm; 95% CI, 0.03 - 0.21 mm; P = .009).

The researchers also analyzed how age impacts carotid IMT, and they found patients with FH had a mean increase of 0.0018 mm (95% CI, –0.0007 to 0.0042 mm) over a control group in 34 studies. For patients with partly treated FH, compared with patients with untreated FH, the mean between-group increase per year was smaller (0.0023 mm; 95% CI, 0.0021 - 0.0025 mm), compared with the control group (0.0104 mm; 95% CI, 0.0100 - 0.0108 mm).

"This sign of residual risk might suggest that more robust cholesterol-lowering treatment and achieving treatment targets, or earlier treatment initiation, is needed to reduce IMT progression to non-FH conditions," the researchers said. "Therefore, we must find and diagnose these patients, and treat them according to current guidelines."

Limitations of the authors' meta-analyses include heterogeneity among studies, differences in IMT measurement protocols, and inclusion of studies with an open-label design. Although randomized clinical trials would be preferable to compare treatment effect, "since statin therapy is indicated in FH patients to reduce [cardiovascular disease], it would be unethical to have a placebo group," they said.

The authors disclosed no relevant financial relationships.

J Clin Lipidol. Published January 31, 2022. Full text

This article originally appeared on MDedge.com, part of the Medscape Professional Network.

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